CHARACTERIZATION OF ENDOGENOUS DNA-ADDUCTS BY LIQUID-CHROMATOGRAPHY ELECTROSPRAY-IONIZATION TANDEM MASS-SPECTROMETRY

Endogenous carcinogens arising from normal metabolism are known to cause modifications to DNA by reacting with bases to form adducts. Malondialdehyde is a web characterized endogenous carcinogen that forms an adduct with 2'-deoxyguanosine. This adduct has been detected in rat and human liver DNA by gas chromatography/electron capture negative-ion chemical ionization mass spectrometry. A method has been developed based on liquid chromatography/electrospray ionization tandem mass spectrometry for the characterization of endogenous DNA adducts. Using this method, it was unequivocally established that the malondialdehyde adduct of 2'-deoxyguanosine was a constituent of human liver DNA. The methodology that has been developed should be applicable to the characterization of other endogenous DNA adducts, There are few structural or biological data available to assess the importance of endogenous DNA adducts as premutagenic lesions responsible for the develop ment of cancer. The availability of methodology based on liquid chromatography/electrospray ionization tandem mass spectrometry for the characterization of DNA adducts should greatly facilitate future studies in this area.